eprintid: 3111
rev_number: 6
eprint_status: archive
userid: 69
dir: disk0/00/00/31/11
datestamp: 2016-02-22 12:17:14
lastmod: 2016-04-06 09:54:41
status_changed: 2016-02-22 12:17:14
type: article
metadata_visibility: show
creators_name: Spina, Salvatore
creators_name: Murrell, Jill R.
creators_name: Huey, Edward D.
creators_name: Wassermann, Eric M.
creators_name: Pietrini, Pietro
creators_name: Baraibar, M.A.
creators_name: Barbeito, A.G.
creators_name: Troncoso, J.C.
creators_name: Vidal, R.
creators_name: Ghetti, Bernardino
creators_name: Grafman, Jordan
creators_id: 
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creators_id: pietro.pietrini@imtlucca.it
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title: Clinicopathologic features of frontotemporal dementia with Progranulin sequence variation
ispublished: pub
subjects: RC0321
divisions: CSA
full_text_status: none
abstract: Background: Frontotemporal lobar degeneration with ubiquitin-immunoreactive (ub-ir) inclusions (FTLD-U) has been associated with frontotemporal dementia (FTD) and ALS. Recently, mutations in Progranulin (PGRN), predicted to cause premature truncation of the PGRN coding sequence, were found in patients with inherited FTLD-U and ub-ir neuronal intranuclear inclusions (NII).Objective: To describe clinical, pathologic, and genetic features of three FTD patients having either a family history of FTD (A.III.1 and B.II.1) or of ALS (C.III.1).Methods: Patients underwent a single clinical assessment, MRI, and 18Ffluorodeoxyglucose PET brain scan. Neuropathologic examination and genetic analyses were carried out.Results: Patients presented clinically with the behavioral variant of FTD. Language dysfunctions were marked with comprehension being particularly affected. Neuroimaging revealed frontotemporal atrophy and glucose hypometabolism, with predominant left-side involvement, in Patients A.III.1 and B.II.1. Subject C.III.1 displayed mild atrophy and symmetric anterior hypometabolism. All patients were neuropathologically diagnosed with FTLD-U. Ub-ir NII were noted in Patients A.III.1 and B.II.1 but were absent in Patient C.III.1. The following PGRN sequence variations were found: IVS6-2A→G (A.III.1), R493X (B.II.1), and R433W (C.III.1). IVS6-2A→G may lead to skipping of exon 7 with consequent frameshift of the coding sequence and premature termination of PGRN translation.Conclusions: We have found two PGRN mutations associated with FTD, in affected individuals who are members of families with possible autosomal dominant FTD. A third PGRN sequence variation (R433W) was found in an FTD patient with family history of ALS.
date: 2007
date_type: published
publication: Neurology
volume: 68
number: 11
publisher: Lippincott Williams & Wilkins
pagerange: 820-827
id_number: 10.​1212/​01.​wnl.​0000254460.​31273.​2d
refereed: TRUE
issn: 0028-3878
official_url: http://www.neurology.org/content/68/11/820.abstract
citation:   Spina, Salvatore and Murrell, Jill R. and Huey, Edward D. and Wassermann, Eric M. and Pietrini, Pietro and Baraibar, M.A. and Barbeito, A.G. and Troncoso, J.C. and Vidal, R. and Ghetti, Bernardino and Grafman, Jordan  Clinicopathologic features of frontotemporal dementia with Progranulin sequence variation.  Neurology, 68 (11).  pp. 820-827.  ISSN 0028-3878      (2007)